Public health and experimental research

Delivered 12th October 1945 By Sir William Savage

The developments in public health over the last 50 years have been mainly based upon the application of scientific research and so largely, if indirectly, on animal experiments. Obviously the whole debt cannot be covered in a single lecture and all that is possible is to illustrate it by examples from various fields.

Control Over Acute Infectious Diseases

Such control has comparatively little to do with improvements in general sanitation but depends on knowledge of causa­tion, methods of dissemination of the organism responsible, control over the spread of infection and the application of methods of immunisation. In pre-bacteriological days clinical studies established many distinct types of infection, but there was still a good deal of confusion and many diseases were not clearly separated. Little was known about the methods of spread and effective control was non-existent. Until bac­teriologists and epidemiologists had established the factors involved in the spread of disease satisfactory progress was impossible. This potent weapon of accurate knowledge is largely due to bacteriology, won by laboratory workers with-animal experiments as an absolutely necessary adjunct. In general it may be said that we now have sufficient knowledge to control the majority of infectious diseases. So, three diseases are selected, each to illustrate different problems of control.

The Enteric Fevers

The deaths from typhoid and paratyphoid fevers in the 1871-75 period were 371 per million of population, falling steadily to 67 in 1911 and to as low as three for 1939 and 1940. The initial decline was largely due to such matters as improved water supplies and drainage. Meanwhile, field investigations and bacteriological studies showed that infected shell-fish and milk were important vehicles of spread. Studies also demonstrated that a proportion of cured cases continued to harbour the typhoid bacillus and became chronic carriers. Armed with this knowledge many outbreaks were shown to originate from such a carrier and it has become clear that, apart from direct contact infection, the chronic carrier is the key to the infection of new cases. Concurrently, it was shown that typhoid and paratyphoid fevers were distinct infections caused by different bacteria and with somewhat different methods of spread. As I showed recently1 in paratyphoid fever the chronic carrier is often less important as an agent of spread than the mild, unrecognised case or a symptomless recently infected person. Spread by food (cream, milk, etc.) is much more common than spread by water.

A more recent development is the recognition that the typhoid and paratyphoid bacilli are distinct and include a number of types which can be differentiated by phage typing. This is enabling the association of a particular outbreak with infection from a carrier to be demonstrated with accuracy and is of great assistance in clearing up the paths of infection. In a recent paper, Bradley2 has worked out with great skill the relationship of 22 cases, mostly in Buckinghamshire, but actually involving five counties, notified over a period of two years. They were all of phage type D (an uncommon type) and all directly associated with a milk producer who was a persistent typhoid carrier on a farm in Wiltshire more than 100 miles from the main cases in Buckinghamshire, the vehicle being milk.

Diphtheria

There has been a marked decline in mortality, but until quite recently no conspicuous decline in the prevalence of the disease. Its control covers three stages.

The first stage was the recognition of the disease as a clinical entity when bacteriological confirmation became possible - although little was known of causation or spread, and no specific method of treatment existed.

The second stage started in 1894 with the introduction of diphtheria antitoxin as a form of specific treatment. The method of spread was recognised as case to case, which could partly be controlled by swabbing and other methods founded on our bacteriological knowledge. The use of antitoxin effected a dramatic reduction in mortality. This was not, however, paralleled by any corre­sponding reduction in the prevalence of diphtheria.

The third stage is the introduction of specific immunisation as a means to eliminate the disease in the area in which it is practised. Introduced in 1926 in U.S.A. and Canada, it only gradually became extensively adopted and the procedure standardised, while in this country it has only been widely practised during the last world war. The results in America, with their longer duration, are excellent. A detailed account of the Canadian figures is given by McKinnon3, and I have only time to mention the figures for Ontario:

Per 100,000 population

Year

Cases

Deaths

Deaths

Incidence

1901

2627

772

35.4

120

1905

2641

503

21.7

114

1910

2559

435

17.5

103

1915

2719

341

12.7

101

1920

5940

745

25.7

205

1925

3031

251

8.1

98

1930

3198

202

6.1

97

1935

361

33

0.9

10

1936

290

31

0.8

8

1937

506

30

0.8

13

1938

234

11

0.3

6

1939

131

13

0.4

4

1940

73

9

0.3

2

In assessing the influence of immunisation upon the incidence of diphtheria it has to be realised that while efficient dosage nearly completely protects the individual, statistical evidence of a general reduction is unlikely until a significant proportion of the population is protected. This may be put as at least 50 per cent, including pre-school and school popula­tions, and personally I put it as rather higher. It is therefore rather early to look for significant reductions but the available figures are entirely encouraging. For example, Stocks4, dealing with the vital statistics for 1943, points out that the deaths from diphtheria decreased from 2,641 in 1941, to 1,827 in 1942, and 1,370 in 1943. This fall was found in the 1-15yrs age group, the number of deaths in the under ones and over 15’s actually increased. Thus suggesting that had it not been for immunisation 1943 would have recorded a rise in total diphtheria mortality instead of a fall.

Whooping Cough.

Whooping cough has only been identifiable over the last few years so exact figures of prevalence are not available, but there is little evidence of any decline in incidence. Greater care in the management of cases has led to a decrease in mortality. Deaths per million have declined from 450-550 over the period 1860-1890 to below 100 from 1923 on­wards. The deaths per million at ages one to five still remain considerable, and from 1936 to 1941 were respectively 382, 330, 221, 221, 128, 475 (1941). Ninety per cent, of the deaths are within the age group under five.

The bacterial cause has been known since 1906, but it was many years before B. pertussis was accepted generally as the causal agent. Whooping cough is difficult to diagnose before spread of infection so it is doubtful whether control by ordinary measures is possible, while general immunisation is probably not worth while. Immunisation of children under five years, and especially under two years, would eliminate nearly all the deaths and the bad after effects. This requires a process of immunisation which is both effective and easy to operate, and so far this is not the case.

These diseases illustrate three contrasts

The enteric fevers being spread mainly by water, milk or shellfish, were markedly reduced by general environmental improvements but only up to a point - continued progress depended upon accurate bacteriological knowledge and its applica­tion. Diphtheria responded not at all to measures of general sanitary improve­ment and the whole cycle of control, reduction in mortality and final elimination turn entirely upon scientific knowledge largely won from animal experiments. Whooping cough is not controlled and only offers the prospect of a great reduction in child mortality when the present valuable scientific work on immunisation becomes administratively practicable on a large scale.

Environmental Improvements

The enormous improvements in our health statistics are due in part to general improvement in the environmental conditions under which we live. The conditions which prevailed when the great Public Health Act of 1875 was passed were so deplorable that the primary need was to remove or improve these bad conditions, by purer water supplies, removal of danger from faulty drainage, better control over food, improved housing, better living standards and a greater attention to healthy living. Such action naturally improved health, but it should not be overlooked that the stimulus to improvement and to some extent the lines those improvements took, were in considerable part derived from the growth of our scientific knowledge, particularly of bacteriology. There is a limit to the benefit which improved standards of living can provide and a study of public health legislation has shown that further advances were associated with the application of exact scientific knowledge to particular problems. This has already been shown for the enteric fevers and can be further illustrated by two other conditions which are especially susceptible to environmental improve­ments, i.e., tuberculosis and the group of conditions we include under infant and maternal welfare.

The incidence of human tuberculosis is markedly influenced by environ­mental factors and their improvement plays a great part in the reduction of tuberculosis. We now know that tuber­culosis is influenced by two factors: the resistance of the individual and the invasive properties of the tubercle bacillus. Resistance is influenced by adequate nutrition and the prevention of debilitating infections, while harmful invasion by the tubercle bacillus is greatly reduced in potency by keeping the dose of infection low. Hence the great importance of isolating advanced cases, removing and treating infective cases in sanatoria, and educating cases at home in anti-infective precautions. We can to a considerable extent apply the scientific knowledge of the laboratory to the prevention of tuberculosis. The decline in tuberculosis mortality is perhaps the most striking statistical fact in relation to public health.

The rates of infantile mortality (i.e., deaths under one year per 1,000 live births) are summarised in the following table:

Period

Infant Mortality Rate

Period

Infant Mortality Rate

1871-75

153

1906-10

117

1876-80

145

1911-15

110

1881-85

139

1916-20

90

1886-90

145

1921-25

76

1891-95

151

1926-30

68

1896-1900

156

1931-35

62

1901-05

138

1936-40

55

The figures show that this rate exhibited no significant decrease until after 1900 and was unaffected by the great improvements in sanitary condition. The phenomenal decline in the infant mortality rate is associated with an improved environment of the infant and not with improvements in general sanitation.

Many of these infant deaths are due to bacterial infections, the Local Government Board special report stated: “It is certain that more than half of infant mortality is due to infection”. A protected environment shields the infant from bacterial infections, especially those which affect the gastro-intestinal and respiratory tracts. This realisation and the ways to implement it are straightforward deductions from bacteriology and experimental research.

Experimental research has proved valuable in the field of maternity and child welfare. From 1911 to 1935 the maternal mortality rate was between 3-8 and 4-6 per 1,000 live births registered, with some fluctuations in good years but no downward trend. Only since 1936 has this rate decreased - puerperal sepsis largely due to the use of sulphonamide drugs and to a better knowledge of the bacterial causes and the practicability of excluding infection. The following table shows the value of experimental research:

Rates per 1,000 live births

Year

Puerperal Sepsis

Other Puerperal Causes

Total Maternal Mortality

1930

1.92

2.48

4.4

1935

1.68

2.42

4.11

1938

0.89

2.19

3.08

1939

1.05

2.17

3.22

1940

0.82

1.88

2.7

1941

0.85

2.01

2.86

1942

0.8

1.76

2.55

1943

0.76

1.61

2.37

1944

0.62

1.38

2

Future progress in preventive medicine depends upon the collection and the use of knowledge of factors which affect health. There are two main sources of acquisition. One is by investigations based upon detailed comparative statistics under varying conditions. The other is by using the experimental method. Both are valuable and neither can be neglected without loss. The statistical method has the disadvantage that often there are too many variables. For example, the seemingly simple problem of the relationship between defective housing and the incidence of tuberculosis cannot readily be statistically determined, as there are many other variables involved, such as poverty. Tuber­culosis itself lowers wage earnings and so causes the cases to gravitate to low-rented houses.

Limited in other ways, experimental research can largely be freed from a multiplicity of variables. For years many of us have been groping from our field studies towards the basic facts of herd immunisation and the influences of sub-lethal infections. It was the work of Topley and his associates, who carried out experiments with controlled populations of infected mice under regulated conditions, with specific types of infection, which statistically demonstrated important conclusions in preventive medicine.

Control Over Food Supplies

Control in the early days of public health was based upon improvements in standards of cleanliness and on the elimination of gross pathological conditions. Significant improvements were achieved but it soon became evident that further progress could result only from the application of exact scientific knowledge, much of it bacterio­logical. This can be illustrated by considering the diseases associated with milk and the problems of food poisoning.

Many diseases are spread through infected milk and a clean milk supply is in no way a guarantee of a safe milk supply. The toll of acute infectious diseases spread by milk, such as enteric fever, para­typhoid fever, diphtheria, scarlet fever and undulant fever, is very considerable, and their prevention is only possible by the application of the exact knowledge which experimental research has made available. In addition the cow, under commercial conditions of over-production, is particularly liable to tuberculosis. Tuberculin tests show that on an average 40 per cent of our milking cows are affected with tuberculosis. Although at any one time only some 1 per cent are excreting tubercle bacilli into the milk this involves an infection of our milk supply of from 5 to 7 per cent. Since we can differentiate between the human and bovine strains it is possible to determine with accuracy the proportions of each clinical variety of human tuberculosis due to the bovine bacillus and of milk (or milk products) origin. This enables us to calculate the annual human tuberculosis deaths of bovine origin. I first did this in 19295, and similar calculations have been made subsequently. The original calculations showed that about 2,000 deaths in England and Wales, mostly in children, are due to the bovine type of the tubercle bacillus. The figure is probably rather lower to-day, possibly only about 1,500 to 1,600.

A good illustration of the value of experimental research in public health is the relationship of mastitis in cows to human infections. Mastitis, in both its acute and chronic forms, is one of the commonest infections affect­ing the cow. Extensive outbreaks of septic sore throat associated with a cow suffering from mastitis occur but are decidedly rare, and in my book, “Milk and the Public Health” (1912), I could only collect particulars of 18 outbreaks in Great Britain. Subsequently, however, in the Hove out­break of 1929-30, there were more than 1,000 cases with 65 deaths. The discrepancy between prevalence in cows and rarity of infection in man is glaring and it took me three years of experimental work (using goats) to work out the relationship. I was able to show that the type of streptococcus which is the ordinary cause of bovine mastitis is harmless to man and that the infections which cause human disease are associated with the implanta­tion of a pathogenic streptococcus of human origin in the cow's udder. This is a comparatively uncommon mishap and accounts for the rarity of outbreaks in man with this origin. New knowledge of streptococci types, not available in 1906-09 when this work was done, has fully con­firmed the accuracy of this view. It is mentioned here as an illustration of the value of experimental research in clearing up public health obscurities.

These various infections that spread through milk are now well recognised, the methods of spread clearly defined and the preventive steps known. That efficient pasteurisation of our milk supply is not compulsory illustrates the point already made that administrative procedure is affected by factors other than scientific knowledge.

In pre-bacteriological days we had no scientific knowledge of the causes of food contamination and the scanty control exercised was largely along wrong lines. We now know a great deal as to the various bacteriological and chemical agencies which cause attacks of food poisoning. This elucida­tion has been mainly a laboratory affair and its ascertainment quite impos­sible without extensive animal experiments. We now know that bacterial food poisoning is not a problem of tainted or incipiently decomposing food but is due to infection of the food with definite specific organisms, such as members of the Salmonella group, Clostridium botulinum, or with staphylococci which can produce enterotoxin. We can now study their reservoirs in nature, and the paths by which they pass from such reservoirs to the food vehicles. For example, we know that the organism causing botulism is a natural soil inhabitant in many countries, that it may gain access to food from soil contamination, that its spores have a resistance to heat which is extremely high and so may survive in canned foods, and that this bacterium only grows under anaerobic condi­tions, Armed with these facts, it has been possible largely to eliminate this type of food poisoning. In the same way very extensive knowledge has been accumulated as to the Salmonella types of bacilli, including their numerous animal sources and the ways various food vehicles may become contaminated with these strains.

These comprehensive investigations have enabled food control to be removed from empirical guidance based upon the physical senses to one founded upon scientific data. Actually the physical senses form a guide which is completely unreliable since in all food poisoning outbreaks except botulism there are no physical changes in the infected food.

Adequate Nutrition

While nutrition, has always held a prominent place in public health, it is only during the last two decades that its paramount importance has been realised. This has eventuated from two lines of inquiry. The first was the discovery in food of hitherto undreamed-of substances (the vitamins) and the recog­nition of the influence of their deficiency upon the health of animals and man. At first only gross deficiency conditions were studied but later it became clear that there was such a thing as comparative deficiency which also could be associated with deviations from health. The basis of all this knowledge was prolonged animal experiments. This work led to the study of deficiencies in mineral constituents, such as calcium, iodine and iron, and it became possible to lay down minimal and optimum daily intakes for both vitamins and these minerals.

Concurrently with work in the laboratory, studies in the public health field demonstrated on the one hand that many sections of the community were not in fact receiving even the minimum daily intakes of essential food components and on the other hand that this deficiency manifested itself in the development of pathological conditions, such as rickets or simple goitre, and less patently in a diminished resistance to infection, night blind­ness, and other conditions not pathologically identifiable as gross lesions.

A great many field experiments have also proved quite conclusively that what we regarded hitherto as good nutrition is not full nutrition and that by the addition to the diet of selected foods rich in these accessory sub­stances it is found that children increase definitely in height and weight and also improve in mental qualities. We have arrived therefore at a new conception of good nutrition, which we may call optimum nutrition, i.e., the maximum nutritional development. This is being translated into administrative action in the great milk in school schemes and in the pro­vision of additional milk and accessory foods for expectant and nursing mothers and for pre-school children.

This and kindred developments are of primary importance since adequate nutrition is probably the greatest single factor affecting the health of a community. As I noted over 30 years ago, in the mining area of Somerset really bad housing and other poor environmental conditions had but little detrimental effect if the standards of nutrition were high. Really adequate nutrition is Public Health Priority No.1 and we largely owe its realisation and its administrative possibility to experimental research.

The Future of Public Health

We are now on the threshold of a third phase in the development of preventive medicine. The first phase was the great drive towards environ­mental improvements with Chadwick and Simon as its pioneers. This effected enormous improvements in health but with its health dividends gradually diminishing as gross conditions were removed. Progress could only be maintained by new methods and the second phase followed. This was largely one of attack on special diseases or conditions, such as tuber­culosis, venereal diseases and the factors we include under maternity and child welfare and by more specialised studies of infectious diseases. The driving force behind this second phase was the more exact knowledge derived from epidemiological and experimental research.

Our widened knowledge permits us to go forward to our third phase which has as its aim the prevention of deviations from health from whatever cause. Such a new orientation implies that a full study of the causation of all dis­eases is within the scope of preventive medicine. This is an enormous claim which demands better machinery of investigation, such as reliable morbidity statistics and accurate records of illnesses, close co-operation with medical practitioners, and detailed studies in workshops as well as in homes. It asks for more and more knowledge as to disease causation and the beginnings of ill-health. Progress along these lines can only be achieved by the application to living conditions of accurate knowledge of health factors and is bound up indissolubly with the progress of medical and scientific research.